Population genetic structure of Schistosoma mansoni and Schistosoma haematobium from across six sub-Saharan African countries: Implications for epidemiology, evolution and control

Gower, Charlotte; Gouvras, Anouk N.; Lamberton, Poppy H. L.; Deol, Arminder K.; Shrivastava, J. L.; Mutombo, Polydor Ngoy; Mbuh, J.V.; Norton, Alice; Webster, Bonnie L.; Stothard, J. Russell; Garba, Amadou; Lamine, Mariama S.; Kariuki, Curtis; Lange, Charles N.; Mkoji, Gerald M.; Kabatereine, Narcis B.; Gabrielli, Albis Francesco; Rudge, James W.; Fenwick, Alan; Sacko, Moussa; Dembelé, Robert; Lwambo, N. J. S.; Tchuenté, Louis-Albert Tchuem; Rollinson, David; Webster, Joanne P.

doi:10.1016/j.actatropica.2012.09.014

Cited by 72 publications

(90 citation statements)

References 51 publications

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“…Genotyping of modest numbers of microsatellite loci (7-12) is widely used for population genetics of schistosomes [34, 35]. In this study we genotyped 14,489 exonic SNPs (one every 1.018 kb on average) segregating in a single genetic cross.…”

Section: Discussionmentioning

confidence: 99%

Efficient linkage mapping using exome capture and extreme QTL in schistosome parasites

et al. 2014

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BackgroundIdentification of parasite genes that underlie traits such as drug resistance and host specificity is challenging using classical linkage mapping approaches. Extreme QTL (X-QTL) methods, originally developed by rodent malaria and yeast researchers, promise to increase the power and simplify logistics of linkage mapping in experimental crosses of schistosomes (or other helminth parasites), because many 1000s of progeny can be analysed, phenotyping is not required, and progeny pools rather than individuals are genotyped. We explored the utility of this method for mapping a drug resistance gene in the human parasitic fluke Schistosoma mansoni.ResultsWe staged a genetic cross between oxamniquine sensitive and resistant parasites, then between two F1 progeny, to generate multiple F2 progeny. One group of F2s infecting hamsters was treated with oxamniquine, while a second group was left untreated. We used exome capture to reduce the size of the genome (from 363 Mb to 15 Mb) and exomes from pooled F2 progeny (treated males, untreated males, treated females, untreated females) and the two parent parasites were sequenced to high read depth (mean = 95-366×) and allele frequencies at 14,489 variants compared. We observed dramatic enrichment of alleles from the resistant parent in a small region of chromosome 6 in drug-treated male and female pools (combined analysis: = 11.07, p = 8.74 × 10-29). This region contains Smp_089320 a gene encoding a sulfotransferase recently implicated in oxamniquine resistance using classical linkage mapping methods.ConclusionsThese results (a) demonstrate the utility of exome capture for generating reduced representation libraries in Schistosoma mansoni, and (b) provide proof-of-principle that X-QTL methods can be successfully applied to an important human helminth. The combination of these methods will simplify linkage analysis of biomedically or biologically important traits in this parasite.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-617) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Efficient linkage mapping using exome capture and extreme QTL in schistosome parasites

et al. 2014

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“…14 Schistosome populations are very genetically heterogeneous 15,16 and genomic characterisation of human schistosomes can be used to establish epidemiological patterns of transmission, including insights into interspecies hybridisation among some schistosome species. For example, in areas with high transmission of both S haematobium and the S bovis parasites of cattle, bidirectional introgressive hybridisation occurs, yielding schistosomes of mixed heritage in people and snails.…”

Section: Introductionmentioning

confidence: 99%

Human schistosomiasis

et al. 2014

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Human schistosomiasis—or bilharzia—is a parasitic disease caused by trematode flukes of the genus Schistosoma. By conservative estimates, at least 230 million people worldwide are infected with Schistosoma spp. Adult schistosome worms colonise human blood vessels for years, successfully evading the immune system while excreting hundreds to thousands of eggs daily, which must either leave the body in excreta or become trapped in nearby tissues. Trapped eggs induce a distinct immune-mediated granulomatous response that causes local and systemic pathological effects ranging from anaemia, growth stunting, impaired cognition, and decreased physical fitness, to organ-specific effects such as severe hepatosplenism, periportal fibrosis with portal hypertension, and urogenital inflammation and scarring. At present, preventive public health measures in endemic regions consist of treatment once every 1 or 2 years with the isoquinolinone drug, praziquantel, to suppress morbidity. In some locations, elimination of transmission is now the goal; however, more sensitive diagnostics are needed in both the field and clinics, and integrated environmental and health-care management will be needed to ensure elimination.

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“…A previous study did not find a relationship between their calculated N e from schistosome offspring populations and allelic richness [19]. However, it appears that their estimates of N e may not have been very accurate because there was no correlation between N e values from the same samples calculated by two techniques and they were estimated with large confidence intervals.…”

Section: Discussionmentioning

confidence: 80%

Non-Invasive Sampling of Schistosomes from Humans Requires Correcting for Family Structure

et al. 2013

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For ethical and logistical reasons, population-genetic studies of parasites often rely on the non-invasive sampling of offspring shed from their definitive hosts. However, if the sampled offspring are naturally derived from a small number of parents, then the strong family structure can result in biased population-level estimates of genetic parameters, particularly if reproductive output is skewed. Here, we document and correct for the strong family structure present within schistosome offspring (miracidia) that were collected non-invasively from humans in western Kenya. By genotyping 2,424 miracidia from 12 patients at 12 microsatellite loci and using a sibship clustering program, we found that the samples contained large numbers of siblings. Furthermore, reproductive success of the breeding schistosomes was skewed, creating differential representation of each family in the offspring pool. After removing the family structure with an iterative jacknifing procedure, we demonstrated that the presence of relatives led to inflated estimates of genetic differentiation and linkage disequilibrium, and downwardly-biased estimates of inbreeding coefficients (FIS). For example, correcting for family structure yielded estimates of FST among patients that were 27 times lower than estimates from the uncorrected samples. These biased estimates would cause one to draw false conclusions regarding these parameters in the adult population. We also found from our analyses that estimates of the number of full sibling families and other genetic parameters of samples of miracidia were highly intercorrelated but are not correlated with estimates of worm burden obtained via egg counting (Kato-Katz). Whether genetic methods or the traditional Kato-Katz estimator provide a better estimate of actual number of adult worms remains to be seen. This study illustrates that family structure must be explicitly accounted for when using offspring samples to estimate the genetic parameters of adult parasite populations.

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Population genetic structure of Schistosoma mansoni and Schistosoma haematobium from across six sub-Saharan African countries: Implications for epidemiology, evolution and control

Cited by 72 publications

References 51 publications

Efficient linkage mapping using exome capture and extreme QTL in schistosome parasites

Efficient linkage mapping using exome capture and extreme QTL in schistosome parasites

Human schistosomiasis

Non-Invasive Sampling of Schistosomes from Humans Requires Correcting for Family Structure

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